Inflammation

Author: Gianpiero Pescarmona
Date: 15/10/2008

Description

Tumor, Rubor, Calor, Dolor

Inflammation is a response of a tissue to injury. It is characterized by increased blood flow to the tissue associated with:

  • swelling,
  • redness
  • increased temperature
  • pain

Symptoms according to the tissue

Treatment of ankylosing spondylitis and extra-articular manifestations in everyday rheumatology practice 2009

Transcriptional triad of survival. PPARs promote mitochondrial proton gradient uncoupling, reduce ROS and increase heat generation, while ensuring safe lipid storage and burning (reducing lipotoxicity), safe carbohydrate storage and reducing need for insulin. They also suppress inflammation. promotes resistance to infections and aids healing, but suppresses incentive salience and increases thermogenesis – it can be said to have general anorexic actions. Also promotes ROS production, both as a signal and as a defence. Response amplified by increasing fat stores. Promotes inflammation. FOXO promotes resistance to oxidative stress, enhances DNA repair, suppresses proliferation, and encourages incentive salience and survival in low food situations – it is thought to be generally orexigenic. Can oppose inflammation.

antagonists

NFkB nice pictures

Functions of NF-kB1 and NF-kB2 in immune cell biology 2004

Cytotoxic pathways of unconjugated bilirubin (UCB), cytokines and bile acids

NCOR

Low Trp like in IL6

Combinatorial roles of nuclear receptors in inflammation and immunity 2006

Cooperative NCoR/SMRT interactions establish a corepressor-based strategy for integration of inflammatory and anti-inflammatory signaling pathways. 2009

Sumoylation of peroxisome proliferator-activated receptor gamma by apoptotic cells prevents lipopolysaccharide-induced NCoR removal from kappaB binding sites mediating transrepression of proinflammatory cytokines. 2008

Abstract

Efficient clearance of apoptotic cells (AC) by professional phagocytes is crucial for tissue homeostasis and resolution of inflammation. Macrophages respond to AC with an increase in antiinflammatory cytokine production but a diminished release of proinflammatory mediators. Mechanisms to explain attenuated proinflammatory cytokine formation remain elusive. We provide evidence that peroxisome proliferator-activated receptor gamma (PPARgamma) coordinates antiinflammatory responses following its activation by AC. Exposing murine RAW264.7 macrophages to AC before LPS stimulation reduced NF-kappaB transactivation and lowered target gene expression of, that is, TNF-alpha and IL-6 compared with controls. In macrophages overexpressing a dominant negative mutant of PPARgamma, NF-kappaB transactivation in response to LPS was restored, while macrophages from myeloid lineage-specific conditional PPARgamma knockout mice proved that PPARgamma transmitted an antiinflammatory response, which was delivered by AC. Expressing a PPARgamma-Delta aa32-250 deletion mutant, we observed no inhibition of NF-kappaB. Analyzing the PPARgamma domain structures within aa 32-250, we anticipated PPARgamma sumoylation in mediating the antiinflammatory effect in response to AC. Interfering with sumoylation of PPARgamma by mutating the predicted sumoylation site (K77R), or knockdown of the small ubiquitin-like modifier (SUMO) * E3 ligase PIAS1 (protein inhibitor of activated STAT1)*, eliminated the ability of AC to suppress NF-kappaB. Chromatin immunoprecipitation analysis demonstrated that AC prevented the LPS-induced removal of nuclear receptor corepressor (NCoR) from the kappaB site within the TNF-alpha promoter. We conclude that AC induce PPARgamma sumoylation to attenuate the removal of NCoR, thereby blocking transactivation of NF-kappaB. This contributes to an antiinflammatory phenotype shift in macrophages responding to AC by lowering proinflammatory cytokine production.

Ions Transport in Inflammation

Changes in ion transport in inflammatory diseases, 2006

Papers Eisenhut inflammatory

RhoA/ROCK signaling pathway

Rho-associated coiled-coil kinase (ROCK) signaling and disease. 2013

  • Abstract The small Rho GTPase family of proteins, encompassing the three major G-protein classes Rho, Rac and cell division control protein 42, are key mitogenic signaling molecules that regulate multiple cancer-associated cellular phenotypes including cell proliferation and motility. These proteins are known for their role in the regulation of actin cytoskeletal dynamics, which is achieved through modulating the activity of their downstream effector molecules. The Rho-associated coiled-coil kinase 1 and 2 (ROCK1 and ROCK2) proteins were the first discovered Rho effectors that were primarily established as players in RhoA-mediated stress fiber formation and focal adhesion assembly. It has since been discovered that the ROCK kinases actively phosphorylate a large cohort of actin-binding proteins and intermediate filament proteins to modulate their functions. It is well established that global cellular morphology, as modulated by the three cytoskeletal networks: actin filaments, intermediate filaments and microtubules, is regulated by a variety of accessory proteins whose activities are dependent on their phosphorylation by the Rho-kinases. As a consequence, they regulate many key cellular functions associated with malignancy, including cell proliferation, motility and viability. In this current review, we focus on the role of the ROCK-signaling pathways in disease including cancer.

rhoa+rock+nf-kb

The vitamin D receptor agonist elocalcitol inhibits IL-8-dependent benign prostatic hyperplasia stromal cell proliferation and inflammatory response by targeting the RhoA/Rho kinase and NF-kappaB pathways. 2009

Attachments
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NCOR1-e-2-ch1.gifgp18/01/2011
NCOR1-e-2-ch2.gifgp18/01/2011
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